Invega Trinza

What Is Invega Trinza?

Invega Trinza (paliperidone palmitate) extended-release, a 3-month injection, is an atypical antipsychotic indicated for the treatment of schizophrenia in patients after they have been adequately treated with Invega Sustenna (1-month paliperidone palmitate extended-release injectable suspension) for at least four months.

What Are Side Effects of Invega Trinza?

Common side effects of Invega Trinza include:

• injection site reactions (redness, swelling, inflammation, hard lump, and pain),
• weight gain,
• headache,
• upper respiratory tract infection,
• urinary tract infection,
• restlessness (akathisia), and
• parkinsonism (tremor, slow movements, muscle rigidity, muscle tightness, postural instability, drooling, stiffness).

Dosage for Invega Trinza

The dose of Invega Trinza should be administered once every 3 months, and is based on the previous dose of Invega Sustenna.

What Drugs, Substances, or Supplements Interact with Invega Trinza?

Invega Trinza may interact with carbamazepine, rifampin, or St. John's Wort. Tell your doctor all medications and supplements you use.

Invega Trinza During Pregnancy or Breastfeeding

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including Invega Trinza, during pregnancy. Neonates exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for undesirable side effects and/or withdrawal symptoms following delivery. This drug passes into breast milk but its effects on a nursing infant are unknown. Consult your doctor before breastfeeding.

Additional Information

Our Invega Trinza (paliperidone palmitate) extended-release Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

 

Invega Trinza Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Tell your doctor right away if you have any of these signs of a serious movement disorder:

• tremors or shaking in your arms or legs;
• uncontrolled muscle movements in your face (chewing, lip smacking, frowning, tongue movement, blinking or eye movement); or
• any new or unusual muscle movements you cannot control.

Call your doctor at once if you have:

• fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness (like you might pass out);
• trouble swallowing;
• a seizure (convulsions);
• breast swelling (in women or men), nipple discharge;
• changes in menstrual periods;
• impotence, or penis erection that is painful or lasts 4 hours or longer;
• weight gain;
• fever, chills, sore throat, mouth sores, feeling light-headed;
• high blood sugar--increased thirst, increased urination, hunger, fruity breath odor; or
• severe nervous system reaction--very stiff (rigid) muscles, high fever, fast or pounding heartbeats, fainting.

Common side effects may include:

• dizziness, drowsiness;
• cold symptoms such as stuffy nose, sneezing, sore throat;
• feeling restless or anxious;
• muscle stiffness, tremors or shaking;
• uncontrolled muscle movements, trouble with walking, balance, or speech;
• abnormal movements of your eyes;
• weight gain;
• upset stomach, constipation;
• fast heart rate; or
• pain or tenderness where the medicine was injected.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Invega Trinza (Paliperidone Palmitate Extended-release Injectable Suspension)

 

Invega Trinza Professional Information

SIDE EFFECTS

The following are discussed in more detail in other sections of the labeling:

• Increased mortality in elderly patients with dementia-related psychosis [see BOX WARNING and WARNINGS AND PRECAUTIONS]
• Cerebrovascular adverse reactions, including stroke, in elderly patients with dementia-related psychosis [see WARNINGS AND PRECAUTIONS]
• Neuroleptic malignant syndrome [see WARNINGS AND PRECAUTIONS]
• QT prolongation [see WARNINGS AND PRECAUTIONS]
• Tardive dyskinesia [see WARNINGS AND PRECAUTIONS]
• Metabolic changes [see WARNINGS AND PRECAUTIONS]
• Orthostatic hypotension and syncope [see WARNINGS AND PRECAUTIONS]
• Falls [see WARNINGS AND PRECAUTIONS]
• Leukopenia, neutropenia, and agranulocytosis [see WARNINGS AND PRECAUTIONS]
• Hyperprolactinemia [see WARNINGS AND PRECAUTIONS]
• Potential for cognitive and motor impairment [see WARNINGS AND PRECAUTIONS]
• Seizures [see WARNINGS AND PRECAUTIONS]
• Dysphagia [see WARNINGS AND PRECAUTIONS]
• Priapism [see WARNINGS AND PRECAUTIONS]
• Disruption of body temperature regulation [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Patient Exposure

The data described in this section include data from two clinical trials. One is a long-term maintenance trial, in which 506 subjects with schizophrenia received several doses of the 1-month paliperidone palmitate extended-release injectable suspension during the open-label phase, of which 379 subjects continued to receive a single injection of INVEGA TRINZA^® during the open-label phase, and 160 subjects were subsequently randomized to receive at least one dose of INVEGA TRINZA^® and 145 subjects received placebo during the double-blind placebo-controlled phase. The mean (SD) duration of exposure during the double-blind phase was 150 (79) days in the placebo group and 175 (90) days in the INVEGA TRINZA^® group. The other is a Phase 1 study (N=308), which included patients with schizophrenia who received a single injection of INVEGA TRINZA^® concomitantly with other oral antipsychotics.

Adverse Reactions In A Double-Blind, Placebo-Controlled (Long-Term Maintenance) Clinical Trial

Commonly Observed Adverse Reactions:

The most common adverse reactions (incidence at least 5% in the open-label phase, or in the INVEGA TRINZA^® group and at least twice the incidence in the placebo group during the double-blind phase) were injection site reaction, weight increased, headache, upper respiratory tract infection, akathisia, and parkinsonism.

Discontinuation of Treatment Due to Adverse Events:

The percentages of subjects who discontinued due to adverse events in the long-term maintenance trial were 5.1% during the open-label phase. During the double-blind phase, no INVEGA TRINZA^®-treated subject and one placebo-treated subject discontinued due to adverse events.

Adverse Reactions Occurring at an Incidence of 2% or More in INVEGA TRINZA^®-Treated Patients:

The safety profile of INVEGA TRINZA^® was similar to that seen with the 1-month paliperidone extended-release injectable suspension. Table 8 lists the adverse reactions reported in a long-term maintenance trial in subjects with schizophrenia.

Table 8. Incidences of Adverse Reactions 2% or More of INVEGA TRINZA^®-Treated Patients (and Greater than Placebo) for the Open-Label and Double-Blind Phases of a Long-Term Maintenance Trial in Patients with Schizophrenia

System Organ Class	Open Label	Double Blind
	Paliperidone Palmitatea	Placebo	INVEGA TRINZA®
	(N=506)	(N=145)	(N=160)
Adverse Reactionb	%c	%c	%c
General disorders and administration site conditions
Injection site reaction	12	0	3
Infections and infestations
Upper respiratory tract infection	5	4	10
Urinary tract infection	<1	1	3
Metabolism and nutrition disorders
Weight increased	10	3	9
Nervous system disorders
Akathisia	5	2	5
Headache	7	4	9
Parkinsonism	5	0	4
Table includes adverse reactions that were reported in 2% or more of subjects in the INVEGA TRINZA® group during the double-blind phase and which occurred at greater incidence than in the placebo group. a During the open-label phase, subjects received several doses of the 1-month paliperidone palmitate extended-release injectable suspension followed by a single dose of INVEGA TRINZA® prior to randomization to either placebo or INVEGA TRINZA® in the subsequent double-blind phase [see Clinical Studies]. b The following terms were combined: Injection site reaction includes Injection site reaction, Injection site erythema, Injection site extravasation, Injection site induration, Injection site inflammation, Injection site mass, Injection site nodule, Injection site pain, Injection site swelling. Weight increased includes Weight increased, Waist circumference increased. Upper respiratory tract infection includes Upper respiratory tract infection, Nasopharyngitis, Pharyngitis, Rhinitis. Akathisia includes Akasthisia, Restlessness. Parkinsonism includes Parkinsonism, Cogwheel rigidity, Drooling, Extrapyramidal disorder, Hypokinesia, Muscle rigidity, Muscle tightness, Musculoskeletal stiffness, Salivary hypersecretion. c Incidence is based on the number of subjects experiencing at least one adverse event, not the number of events.

Demographic Differences

An examination of population subgroups in the long-term maintenance trial did not reveal any evidence of differences in safety on the basis of age, gender, or race alone; however, there were few subjects 65 years of age and older.

Extrapyramidal Symptoms (EPS)

Data from the long-term maintenance trial provided information regarding EPS. Several methods were used to measure EPS: (1) the Simpson-Angus global score which broadly evaluates parkinsonism, (2) the Barnes Akathisia Rating Scale global clinical rating score which evaluates akathisia, (3) the Abnormal Involuntary Movement Scale scores which evaluates dyskinesia, and (4) use of anticholinergic medications to treat EPS (Table 9), and (5) incidence of spontaneous reports of EPS (Table 10).

Table 9. Extrapyramidal Symptoms (EPS) Assessed by Incidence of Rating Scales and Use of Anticholinergic Medication

Scale	Percentage of Subjects
	Open-label Phase	Double-blind Phase
	Paliperidone Palmitatea	Placebo	INVEGA TRINZA®
	(N=506) %	(N=145) %	(N=160) %
Parkinsonismb	6	3	6
Akathisiac	3	1	4
Dyskinesiad	1	3	3
Use of Anticholinergic Medicationse	11	9	11
a During the open-label phase, subjects received several doses of the 1-month paliperidone palmitate extended-release injectable suspension followed by a single dose of INVEGA TRINZA® [see Clinical Studies ]. b For Parkinsonism, percent of subjects with Simpson-Angus Total score > 0.3 at any time (Global score defined as total sum of items score divided by the number of items) c For Akathisia, percent of subjects with Barnes Akathisia Rating Scale global score ≥ 2 at any time d For Dyskinesia, percent of subjects with a score ≥ 3 on any of the first 7 items or a score ≥ 2 on two or more of any of the first 7 items of the Abnormal Involuntary Movement Scale at any time e Percent of subjects who received anticholinergic medications to treat EPS

Table 10. Extrapyramidal Symptoms (EPS)-Related Events by MedDRA Preferred Term

EPS Group	Percentage of Subjects
	Open-label Phase	Double-blind Phase
	Paliperidone Palmitatea	Placebo	INVEGA TRINZA®
	(N=506) %	(N=145) %	(N=160) %
Overall percentage of subjects with EPS-related adverse events	10	3	8
Parkinsonism	4	0	4
Hyperkinesia	5	2	5
Tremor	2	0	1
Dyskinesia	<1	1	1
Dystonia	1	0	1
a During the open-label phase, subjects received several doses of the 1-month paliperidone palmitate extended-release injectable suspension followed by a single dose of INVEGA TRINZA® [see Clinical Studies]. Parkinsonism group includes: Cogwheel rigidity, drooling, extrapyramidal disorder, hypokinesia, muscle rigidity, muscle tightness, musculoskeletal stiffness, parkinsonism Hyperkinesia group includes: Akathisia, restlessness Dystonia group includes: Blepharospasm, dystonia, muscle spasms

After injection of INVEGA TRINZA^® in the open-label phase, 12 (3.2%) subjects had EPS that were new or worsened in severity, with events under the groupings of hyperkinesia (1.6%) and parkinsonism (1.3%) being the most common. After injection of INVEGA TRINZA^® in the open-label or double-blind phases, one subject discontinued from the open-label phase due to restlessness.

An examination of the time to EPS during the double-blind phase showed no clustering of these events at visits that would be expected to correspond to median peak plasma concentrations of paliperidone for subjects randomized to INVEGA TRINZA^®.

Dystonia

Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during the first few days of treatment. Dystonic symptoms include: spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue. While these symptoms can occur at low doses, they occur more frequently and with greater severity with high potency and at higher doses of first generation antipsychotic drugs. An elevated risk of acute dystonia is observed in males and younger age groups.

Pain Assessment And Local Injection Site Reactions

Investigator ratings of injection site. Redness and swelling were observed in 2% or less of subjects in the INVEGA TRINZA^® and placebo groups during the double-blind phase of the long-term maintenance study, and were rated mild based on investigator ratings using a 4-point scale (0=absent; 1=mild; 2=moderate; 3=severe). There were no reports of induration in either group during the double-blind phase, and no subjects discontinued due to INVEGA TRINZA^® injection.

Subject ratings of injection site pain

Subject evaluations of injection pain during the double-blind phase also were similar for placebo and INVEGA TRINZA^®.

Subject ratings of injection site pain in the single-dose Phase 1 study allowed for assessment of the temporal course of injection site pain. Residual injection pain peaked 1 or 6 hours after injection, and trended downward 3 days after the injection. Deltoid injections were numerically more painful than gluteal injections, although most pain ratings were below 10 mm on a 100-mm scale.

Other Adverse Reactions Observed During The Clinical Trial Evaluation Of INVEGA TRINZA^®

The following additional adverse reactions were identified in the long-term maintenance trial. The following list does not include reactions: 1) already listed in previous tables or elsewhere in labeling, 2) for which a drug cause was remote, 3) which were so general as to be uninformative, 4) which were not considered to have significant clinical implications, or 5) occurred at an incidence lower than that of placebo-treated patients.

Cardiac disorders: tachycardia

Gastrointestinal disorders: nausea, vomiting

Metabolism and nutrition disorders: hyperinsulinemia

Psychiatric disorders: anxiety

Additional Adverse Reactions Reported In Clinical Trials With The 1-Month Paliperidone Palmitate Extended-Release Injectable Suspension

The following is a list of additional adverse reactions that have been reported in clinical trials with the 1-month paliperidone palmitate extended-release injectable suspension:

Cardiac disorders: atrioventricular block first degree, bradycardia, bundle branch block, palpitations, postural orthostatic tachycardia syndrome

Ear and labyrinth disorders: vertigo

Eye disorders: eye movement disorder, eye rolling, oculogyric crisis, vision blurred

Gastrointestinal disorders: abdominal discomfort/abdominal pain upper, diarrhea, dry mouth, toothache

General disorders and administration site conditions: asthenia, fatigue

Immune system disorders: hypersensitivity

Investigations: electrocardiogram abnormal

Metabolism and nutrition disorders: decreased appetite, increased appetite

Musculoskeletal and connective tissue disorders: back pain, myalgia, pain in extremity, joint stiffness, muscle spasms, muscle twitching, nuchal rigidity

Nervous system disorders: bradykinesia, cerebrovascular accident, convulsion, dizziness, dizziness postural, dysarthria, hypertonia, lethargy, oromandibular dystonia, psychomotor hyperactivity, syncope

Psychiatric disorders: agitation, nightmare

Reproductive system and breast disorders: breast discharge, erectile dysfunction, gynecomastia, menstrual disorder, menstruation delayed, menstruation irregular, sexual dysfunction

Respiratory, thoracic and mediastinal disorders: cough

Skin and subcutaneous tissue disorders: drug eruption, pruritus, pruritus generalized, rash, urticaria

Vascular disorders: hypertension

Additional Adverse Reactions Reported In Clinical Trials With Oral Paliperidone

The following is a list of additional adverse reactions that have been reported in clinical trials with oral paliperidone:

Cardiac disorders: bundle branch block left, sinus arrhythmia

Gastrointestinal disorders: abdominal pain, constipation, flatulence, small intestinal obstruction

General disorders and administration site conditions: edema, edema peripheral

Immune system disorders: anaphylactic reaction

Musculoskeletal and connective tissue disorders: arthralgia, musculoskeletal pain, torticollis, trismus

Nervous system disorders: grand mal convulsion, parkinsonian gait, transient ischemic attack

Psychiatric disorders: sleep disorder

Reproductive system and breast disorders: breast engorgement, breast tenderness/breast pain, retrograde ejaculation

Respiratory, thoracic and mediastinal disorders: nasal congestion, pharyngolaryngeal pain, pneumonia aspiration

Skin and subcutaneous tissue disorders: rash papular

Vascular disorders: hypotension, ischemia

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of paliperidone; because these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: angioedema, ileus, swollen tongue, thrombotic thrombocytopenic purpura, urinary incontinence, and urinary retention.

Cases of anaphylactic reaction after injection with the 1-month paliperidone palmitate extended-release suspension have been reported during postmarketing experience in patients who have previously tolerated oral risperidone or oral paliperidone.

Paliperidone is the major active metabolite of risperidone. Adverse reactions reported with oral risperidone and risperidone long-acting injection can be found in the Adverse Reactions (6) sections of the package inserts for those products.

Read the entire FDA prescribing information for Invega Trinza (Paliperidone Palmitate Extended-release Injectable Suspension)